This application describes initial studies to determine the potential usefulness of the polycation hexadimethrine (HDM) as an anti-tumor drug. This polycation significantly stimulated (50%) the DNA-synthetic response of normal lymphocytes, while the proliferation of the murine leukemia, L1210, was inhibited. Other polycations tested, including various molecular weight poly-L-lysines, poly-D-lysine, protamine, and compound 48/80 did not have this effect. In preliminary in vivo experiments. HDM had no effect on the rejection of histoincompatible skin grafts by Balb/C mice. HDM did inhibit the growth of the L1210 leukemia in DBA/2J mice and increased the life span of tumor-bearing mice in a dose-dependent manner. These results suggest that HDM, or structurally similar polycations may be developed into useful anti-tumor compounds. Such development would contribute to programs in the Division of Cancer Treatment, N.C.I. The goal of this SBIR-phase I proposal is two-fold, firstly, to determine the most active molecular weight range of the HDM. This is important as the commercial preparations range from 600 to over 8,000 daltons. Secondly, the in vivo systems will be expanded to include the ascites form of the L1210 and the P388 leukemia, and several non-leukemic tumors for comparison. The expected S.B.I.R. program Phase II continuation of this project would involve the development of detailed dose-response curves for the most active molecular weight fractions determined in the Phase I studies. Structural alterations of the HDM would also be considered both by direct synthesis of analogues and by comparisons of other polycations in the in vivo systems. These studies should lead to the development of structural or molecular weight analogues to the HDM which would be useful in the treatment of neoplastic diseases. Such analogues would be new compounds and as such would have a high probability of patentability. This would lead to private funding of future toxicological and efficacy testing necessary to an Investigational New Drug Application with the Food and Drug Administration and development of new polycation anti-cancer drugs.